Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies

Autor: Katarzyna Janowska, Guillaume Stewart-Jones, Ye Zhou, Bhavna Hora, Naomi Bronkema, Tyler Evangelous, Alberto Bartesaghi, John R. Perfect, Hui Li, Robert A. Seder, Michael S. Seaman, Celia C. LaBranche, A. Yousef Abuahmad, Jordan Sprenz, Joseph R. Francica, M. Anthony Moody, Baptiste Aussedat, S. Munir Alam, Garnett Kelsoe, Sampa Santra, Barton F. Haynes, Richard Laga, Priyamvada Acharya, Katayoun Mansouri, Daniela Fera, Victoria Stalls, Nathan I. Nicely, Margaret Deyton, Allen L. Hsu, Madison Berry, George M. Shaw, Megan Kopp, William E. Walkowicz, David C. Montefiori, Gregory D. Sempowski, Matthew S. Lee, Sophie M. C. Gobeil, Mario J. Borgnia, Todd Bradley, Thomas H. Oguin, R. Ryan Meyerhoff, Robert Parks, Kevin Wiehe, Mattia Bonsignori, Peter D. Kwong, Kartik Manne, Geoffrey M. Lynn, Rory Henderson, Robert J. Edwards, Wilton B. Williams, Andrew Foulger, Kevin O. Saunders
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Glycosylation
HIV Infections
marginal zone B cells
HIV Antibodies
medicine.disease_cause
Immunoglobulin D
Epitope
chemistry.chemical_compound
Epitopes
0302 clinical medicine
FDG Abs
glycan-dependent Ab binding
0303 health sciences
B-Lymphocytes
Vaccines
biology
Immunoglobulin Fab Fragments
env Gene Products
Human Immunodeficiency Virus
virus diseases
Spike Glycoprotein
Coronavirus
Simian Immunodeficiency Virus
natural Abs
Antibody
Dimerization
Glycan
Receptors
Antigen
B-Cell
SARS-CoV-2 spike glycans
IgM-memory B cells
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Antigen
Polysaccharides
medicine
Animals
Humans
030304 developmental biology
SARS-CoV-2
HIV-1 Env glycans
COVID-19
Simian immunodeficiency virus
Virology
Antibodies
Neutralizing
Macaca mulatta
carbohydrates (lipids)
chemistry
biology.protein
HIV-1
Fab dimerization
030217 neurology & neurosurgery
Broadly Neutralizing Antibodies
Zdroj: Cell
ISSN: 1097-4172
0092-8674
Popis: Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (VH) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgM+IgD+CD27+, thus suggesting that they originated from a pool of antigen-experienced IgM+ or marginal zone B cells.
Graphical abstract
Structural and functional analyses identify a category of glycan-reactive antibodies in macaques and humans that are marked by the dimerization of the antigen-binding fragment. These antibodies are involved in HIV neutralization and also recognize the S2 protein of SARS-CoV-2.
Databáze: OpenAIRE
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